The results of the proposed studies will provide a better understanding of the biology and immunology of Toxoplasma gondii and the epidemiology, diagnosis and treatment of acute and chronic congenital and acquired toxoplasmosis, and the unique role of Toxoplasma in infection in the immunologically compromised host. Genetic variation and virulence of cloned "strains" of Toxoplasma will be studied and comparisons will be made of the molecular biology (DNA hybridization) and antigenic structure of Toxoplasma to related and unrelated protozoa. Prospective studies of the incidence of congenital toxoplasmosis will be carried out by studying seroconversion during pregnancy. Prospective, as well as retrospective, studies of the incidence of retinochoroiditis in acquired infection will also be made. Presently available diagnostic procedures will be improved and new ones developed, including a radioimmunoassay for circulating antigen, increasing the sensitivity of the IgM-IFA test, determining the feasibility of demonstrating Toxoplasma in brain biopsy material, and further characterization of the histopathology of the lymphadenopathic form. The site of circulating Toxoplasma in patients with parasitemia will be determined and the dynamics of endogenous reinfection will be studied in the normal and immunosuppressed host. Genetic variation in host resistance to Toxoplasma will be studied in inbred and congenic strains of mice. The role of the lymphocyte-macrophage system in resistance to Toxoplasma will be studied, including: the nature of the lymphocyte response to Toxoplasma, suppression of specific lymphocyte recognition of Toxoplasma and activation of macrophages during acute human toxoplasmosis, the specificity of macrophage recognition of Toxoplasma, and the role of alveolar macrophages in resistance to Toxoplasma. The efficacy of newer antimicrobials and their synergistic effects will be evaluated in animal models.